Reshaping children’s HIV treatment

Data presented at the 33rd Conference on Retroviruses and Opportunistic Infections (CROI 2026) in Denver offered the promise of addressing adherence and viral suppression in children and adolescents, through long-acting injectable ART and even therapy to control HIV without ART. 

Some children stay undetectable after stopping ART

One-third of children with HIV who received very early ART had no detectable virus in their body for at least 12 weeks after stopping treatment, according to findings from a small South African study shared at CROI. The results suggest that children initiating HIV treatment at a very early age may later be able to control the virus without therapy, according to presenting author Gabriela Cromhout, MBChB, MSc, a physician and HIV cure researcher at the University of KwaZulu-Natal.

Data presented by Cromhout were inspired by a larger, earlier study. Intrigued by the Mississippi Baby case, where a child’s HIV viral load remained undetectable for more than two years without ART, Cromhout’s team hypothesized that very early ART initiation might limit latent reservoir formation and increase the chance for ART-free remission in some children. To test this theory, researchers established the Ucwaningo Lwabantwana Cohort study in KwaZulu-Natal, South Africa, enrolling 330 mother-infant pairs who were living with HIV. All children began receiving ART within three weeks of birth. 

“The aim was to define mechanisms contributing to undetectable HIV, DNA loads and ART-free remission or cure,” Cromhout said. Those results, published in 2024, found that, among children who had discontinued treatment, five boys maintained undetectable viral loads without ART. 

Intrigued by the findings, Cromhout and colleagues developed another study, which they named Azaphile, purposely stopping ART in children to see whether they experienced viral rebound. 

The Azaphile study was small: Researchers monitored 19 children (47% were boys, with a median age of 59 months) who started ART within 21 days of birth (median of 10 days) but stopped at less than three years old. To qualify for treatment interruption, children had to be older than 3 years, have a plasma viral load below 30 copies/mL for at least 2 years, CD4 counts above 500 (for those over five years) or above 750 (for children 36–59 months). To participate, children also needed low DNA viral loads (below 20 copies per million).

Of the 19 enrolled, six children (32%) maintained undetectable viral loads for at least 12 weeks. Thirteen children rebounded within six weeks, however. Of the six children who stayed undetectable for 12 weeks, three rebounded, at 4, 8, 18 and 24 months after treatment interruption. The other three remained suppressed through the study.

Cromhout put Azaphile study results in the context of adult viral rebound studies, where 96% of adults experience viral rebound before 12 weeks of treatment interruption. “Which makes the fact that 32% of participants achieving [no viremia] for more than 12 weeks in our study all the more notable,” Cromhout said.  She concluded by saying that the results show that, while children have a greater potential to be cured of HIV than adults, it is not entirely clear why. One possible reason: children’s viral reservoir, which is what makes HIV so challenging to cure in adults, is very small. Crumhout said this small reservoir, in addition to early ART introduction, may help children’s immune systems fight off opportunistic infections. It is also not clear whether any of the children would have remained undetectable without early ART. 

“Based on adult and non-human primate studies,” Cromhout added, “we hypothesize that greater numbers of very early treated children would achieve remission following bNAb (broadly neutralizing antibodies) interventions, and this is something we are hoping to do in the future.” 

Controlling HIV using combination bNAbs, without ART, in children

Results from one study, presented in the same CROI 2026 session, did test how bNAbs boost viral control for children. bNAbs, specialized proteins that are either generated by the immune system, or developed in labs, neutralize highly-mutating viruses like HIV-1 and SARS CoV-2 by targeting unchanging regions of the virus and thus blocking infection and reducing viral loads. 

Two presenters shared results from the IMPAACT 2042/Tatelo Plus study, which is exploring long-acting treatment options for children living with HIV and for strategies for boosting viral control, with or without ART. 

Phase 1 results of the study showed that, without phenotypic pre-screening, 44% of children who started ART soon after birth maintained low HIV RNA (fewer than 40 copies/mL) through 24 weeks while receiving bNAbs added to ART. 

In the current IMPAACT 2042/Tatelo Plus study, researchers are evaluating, in four steps, whether more children can maintain higher viral suppression by pre-screening them for bNAb susceptibility or biomarkers for HIV replication, and by using broader and more potent bNAbs—without ART. Eligibility criteria included children with HIV RNA fewer than 40 copies per mL for at least 24 weeks prior to entry into the study. Participants had a median age of nine years and all had initiated ART within five days after birth. 

Results of step one, presented in two posters (839, 840), indicated that infusions of PGDM1400LS, PGT121.414.LS and VRC07-523LS were safe and well-tolerated in children with HIV in Botswana who were treated early, using phenotypic susceptibility testing. Researchers found that six (75%) of eight participants were either fully or partly susceptible to at least two bNABs, which allowed them entry to the next study phase.

In step two, participants were susceptible to at least two of the three bNAbs stopped ART and continued to receive bNAbs only. In presenting findings from children who completed the bNAb-only treatment, Gbolahan Ajibola, MB, BS, MPH, MSc, from the Botswana Harvard AIDS Partnership, said all participants had excellent viral suppression at the time of entry to the bNAb-only step. All participants stopped ART and completed the full 24 weeks of bNAb-only treatment without missed doses. There were no grade three or four adverse events. Importantly, bNAb-only treatment did not result in virological failure. 

“We’re happy to report that HIV RNA remained below 40 copies/mL in all participants throughout the entire 24 weeks period,” Ajibola said. 

In step three, which is ongoing, researchers will perform analytic treatment interruption to evaluate viral control without ART or bNAbs. In step four, ART will be restarted and researchers will evaluate long-term safety, including development of bNAb resistance and anti-drug antibodies to bNAbs. 

Ajibola noted some limitations of the study. Participants were selected based on early ART initiation and other favorable characteristics, which may not be generalizable to other children with HIV. Also, the bNAb-only treatment used a non-randomized design, and because of that, “it is possible that some of these children may control the virus without the need for bNAbs,” Ajibola said. 

In conclusion, Ajibola said, “a combined approach using phenotypic screening and biomarker criteria offers a practical first step for trials of bNAbs to promote drug-free [HIV] remission in children.”

DTG/3TC could reduce pill burden for children

While adults have recently benefited from two-drug treatments, evidence for efficacy of simpler regimens for kids has been slow to come. And with everyone, but especially with children, fewer pills can increase all-important adherence. 

The D3/Penta 21 trial enrolled 386 children and adolescents across Uganda, South Africa, Thailand, Spain and the U.K. to make sure the regimen was safe and simpler, but equally effective. Anna Turkova, MD, chief investigator for D3/Penta 21, presented week 96 results of the non-inferiority trial of two-drug regimen dolutegravir/lamivudine (DTG/3TC). The conclusion: DTG/3TC is just as effective as the standard three-drug therapy at keeping the virus suppressed, as well as being slightly more favored by kids. 

Participants, all virologically suppressed for at least six months with a median age of 8.3 years, were stratified by age groups—2–6 years, 6–12 and 12–15—and randomized into two arms. The first arm was DTG/3TC, and the second arm was DTG plus 2 NRTIs. The smallest children were given dispersible tablets; bigger kids had either dispersible tablets or adult film-coated tablets.

The safety profile and tolerability were similar in both arms. In rare cases where virus levels rose slightly, most children in both arms returned to suppressed levels by the end of two years. Few children switched regimens: seven (4%) in the DTG/3TC arm switched to three-drug regimens, and 14 (7%) in the DTG/3DR arm switched to the two-drug regimen. 

Satisfaction with treatment was high in both arms though slightly higher in the DTG/3TC arm. Besides reducing the pill burden, transitioning virologically suppressed children to DTG/3TC can save money, around $145 per child per year. “Children who are virologically suppressed on their first-line treatments can safely be switched to DTG/3TC,” Turkova said.

Adolescents with HIV overwhelmingly choose injectable ART

Also at CROI 2026, ViiV Healthcare shared 96-week results from the 2017 IMPAACT (MOCHA) study, which, in addition to showing that long-acting Cabenuva (cabotegravir/rilpivirine) maintained very high viral suppression among youth ages 12–18 years, that 100% favored this treatment over oral ART by the end of the study. 

Results showed 94.4% of virologically suppressed adolescents ages 12–18 years who switched from daily oral HIV treatment to Cabenuva every two months maintained viral suppression at week 96, with no confirmed virologic failures.

End of study results showed that CAB + RPV given every two months maintained viral suppression (94.4%) with no confirmed virologic failures. At all weeks evaluated, greater than 97% preferred long-acting injections over daily oral antiretroviral therapy. For those who competed all 96 weeks, all (100%) preferred injections over daily oral therapy. 

The long-acting regimen was well tolerated, with 42% experiencing drug-related adverse events (AE), the most common of which were cough (31.9%), headache (26.4%) and upper respiratory tract infections (20.1%). Of 142 participants having received at least one injection, 37% reported mild to moderate injection site pain that typically resolved within one week. 

Presenting the results, Aditya Gaur, MD, a doctor at St. Jude Children’s Research Hospital and co-lead investigator of IMPAACT 2017 (MOCHA) said that the majority of this cohort has lived their life knowing HIV. “This was the first opportunity they had to stop their oral medications and take and go on to injections,” Gaur said. Moving to a brief clinic visits every two months can help reduce the daily reminder of HIV, he added.